1-209626996-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000228.3(LAMB3):c.1486-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 1,545,726 control chromosomes in the GnomAD database, including 14,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 2720 hom., cov: 33)

Exomes 𝑓: 0.064 ( 11352 hom. )

Consequence

LAMB3
NM_000228.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.95

Publications

4 publications found

Variant links:

Genes affected

LAMB3 (HGNC:6490): (laminin subunit beta 3) The product encoded by this gene is a laminin that belongs to a family of basement membrane proteins. This protein is a beta subunit laminin, which together with an alpha and a gamma subunit, forms laminin-5. Mutations in this gene cause epidermolysis bullosa junctional Herlitz type, and generalized atrophic benign epidermolysis bullosa, diseases that are characterized by blistering of the skin. Multiple alternatively spliced transcript variants that encode the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

LAMB3 Gene-Disease associations (from GenCC):

junctional epidermolysis bullosa
Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
junctional epidermolysis bullosa Herlitz type
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, Laboratory for Molecular Medicine
junctional epidermolysis bullosa, non-Herlitz type
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, Ambry Genetics
amelogenesis imperfecta type 1A
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
amelogenesis imperfecta type 1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
generalized junctional epidermolysis bullosa non-Herlitz type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LAMB3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-209626996-C-T is Benign according to our data. Variant chr1-209626996-C-T is described in ClinVar as Benign. ClinVar VariationId is 255585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMB3	NM_000228.3 link	c.1486-18G>A		intron_variant	Intron 12 of 22	ENST00000356082.9	NP_000219.2	Q13751A0A0S2Z3R6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAMB3	ENST00000356082.9 link	c.1486-18G>A	intron_variant	Intron 12 of 22	1	NM_000228.3	ENSP00000348384.3	Q13751
LAMB3	ENST00000367030.7 link	c.1486-18G>A	intron_variant	Intron 12 of 22	1		ENSP00000355997.3	Q13751
LAMB3	ENST00000391911.5 link	c.1486-18G>A	intron_variant	Intron 11 of 21	1		ENSP00000375778.1	Q13751

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19759

AN:

152012

Hom.:

2705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.578

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.0165

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0277

Gnomad OTH

AF:

0.117

GnomAD2 exomes

AF:

0.132

AC:

30749

AN:

232404

AF XY:

0.119

show subpopulations

Gnomad AFR exome

AF:

0.275

Gnomad AMR exome

AF:

0.298

Gnomad ASJ exome

AF:

0.0199

Gnomad EAS exome

AF:

0.583

Gnomad FIN exome

AF:

0.0203

Gnomad NFE exome

AF:

0.0274

Gnomad OTH exome

AF:

0.0919

GnomAD4 exome

AF:

0.0643

AC:

89672

AN:

1393596

Hom.:

11352

Cov.:

AF XY:

0.0638

AC XY:

44439

AN XY:

696240

show subpopulations

African (AFR)

AF:

0.286

AC:

9181

AN:

32136

American (AMR)

AF:

0.287

AC:

12484

AN:

43440

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

471

AN:

25564

East Asian (EAS)

AF:

0.581

AC:

22450

AN:

38626

South Asian (SAS)

AF:

0.110

AC:

9237

AN:

83920

European-Finnish (FIN)

AF:

0.0208

AC:

1092

AN:

52556

Middle Eastern (MID)

AF:

0.0747

AC:

425

AN:

5690

European-Non Finnish (NFE)

AF:

0.0276

AC:

29083

AN:

1053680

Other (OTH)

AF:

0.0905

AC:

5249

AN:

57984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

3493

6986

10480

13973

17466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1624

3248

4872

6496

8120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.130

AC:

19823

AN:

152130

Hom.:

2720

Cov.:

AF XY:

0.132

AC XY:

9826

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.267

AC:

11055

AN:

41474

American (AMR)

AF:

0.185

AC:

2834

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0167

AC:

AN:

3466

East Asian (EAS)

AF:

0.577

AC:

2966

AN:

5136

South Asian (SAS)

AF:

0.118

AC:

571

AN:

4824

European-Finnish (FIN)

AF:

0.0165

AC:

175

AN:

10618

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0277

AC:

1884

AN:

67988

Other (OTH)

AF:

0.120

AC:

254

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

729

1458

2186

2915

3644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

204

408

612

816

1020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0692

Hom.:

192

Bravo

AF:

0.155

Asia WGS

AF:

0.310

AC:

1079

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Junctional epidermolysis bullosa, non-Herlitz type

Benign:1

Jul 08, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Amelogenesis imperfecta type 1A

Benign:1

Jul 08, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Junctional epidermolysis bullosa gravis of Herlitz

Benign:1

Jul 08, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.0090

(source)

DANN

Benign

0.68

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over